Identification of mice that have altered responses to phosphorylcholine (PC) antigens will facilitate the understanding of the genetic control of immune responses. Most inbred strains produce anti-PC antibodies of limited heterogeneity involving three dominant VL-VH pairs. In the BALB/c however, anti-PC antibodies are predominantly of the VHT15-VK22 idiotype and at the DNA level have been shown to be controlled by a single gene. In other strains there are equal proportions of anti-PC antibodies of the three clonotypes. It has been shown that anti-PC response is regulated by both cellular and humoral mechanisms such as recognition of idiotypes by Th MHC and Th Id helper cells or by suppression of anti-Id antibody resulting in an altered anti-PC response. Recently a population of wild mice designated CNV were found which failed to make anti-PC antibodies upon immunization with various PC containing antigens. When CNV mice were mated to C.B20, an inbred responder strain, 82% of the F1 failed to give an anti-PC responses suggesting a dominant PC gene of CNV origin. Analysis of F2 progeny of the PC hybrids showed that mice homozygous for the CNV allotypes were PC whereas F2 mice (CNV X C.B20) heterozygous for both allotypes and mice homozygous for C.B20 allotype expressed both PC and PC phenotypes suggesting a second regulatory gene that segregates independently and is not linked to allotype.